Predictive Value of Microfilariae-Based Stop-MDA Thresholds After Triple Drug Therapy With IDA Against Lymphatic Filariasis in Treatment-Naive Indian Settings

Abstract Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low.


Figure S2 .
Figure S2.Receiver-operator characteristic (ROC) curves for two different age groups 1 year post-MDA (TAS-1), when elimination was defined within 20 years post-MDA.The panels in the top two rows represent MDA with IDA and the bottom ones MDA with DA.

Figure S3 .
Figure S3.Positive predictive value (PPV) of TAS-1 for elimination of LF for different values of MDA duration and coverage.Elimination was defined as zero mf prevalence 20 years after the last MDA round.PPVs were calculated as a function of the stop-MDA threshold for prevalence of infection (horizontal axis) in the age groups 5+ (black curve) and 15+ (magenta curve).The panels in the top two rows represent MDA with IDA and the bottom two rows represent MDA with DA.We assumed a sample size of 400.

Figure S4 .
Figure S4.Positive predictive value (PPV) of TAS-1 for elimination of LF for different values of MDA duration when coverages were lumped together for different age groups.Elimination was defined within 20 years post-MDA.PPVs were calculated as a function of the stop-MDA threshold for prevalence of infection (horizontal axis) in the age groups 5+ (black curve) and 15+ (magenta curve).The top panels represent MDA with IDA and the bottom panels represent DA.The sample size was 400.

Figure S5 .
Figure S5.Positive predictive value (PPV) of TAS-1, when elimination was defined within 20 and 50 years post-MDA, for 65% MDA coverage.The different panels show two different drug regimens and MDA durations.PPVs were calculated as a function of the stop-MDA threshold for prevalence of infection (horizontal axis) in the age groups 5+.The top panels represent MDA with IDA and the bottom ones represent DA.The sample size was 400.

Figure S6 .
Figure S6.Positive predictive value (PPV) of TAS-1, TAS-2, and TAS-3 for elimination of LF for different values of MDA duration and coverage.Elimination was defined as zero mf prevalence 20 years after the last MDA round.PPVs were calculated as a function of the stop-MDA threshold for prevalence of infection in the age group 5+ (horizontal axis).For TAS-2 and TAS-3, PPVs are conditional on all previous TAS-es being passed with the same prevalence threshold.TAS-1, 2, and 3 were scheduled 1, 3, and 5 years post-MDA, so that the gap between consecutive TAS-es was 2 years.The panels in the top two rows represent MDA with IDA and the bottom two represent DA.For each TAS, we assumed a sample size of 400.

Figure S7 .
Figure S7.Positive predictive value (PPV) of TAS-1, TAS-2, and TAS-3 for elimination of LF following MDA for 3 years at 65% coverage.Elimination was defined as zero mf prevalence 20 years after the last MDA round.PPVs were calculated as a function of the stop-MDA threshold for prevalence of infection in the age group 5+ (horizontal axis).For TAS-2 and TAS-3, PPVs are conditional on all previous TAS-es being passed with the same prevalence threshold.We considered two situations for the surveys: (i) TAS-1, 2, and 3 being scheduled 1, 3, and 5 years post-MDA (black curves) and (ii) TAS-1, 2, and 3 being scheduled 3, 5, and 7 years post-MDA (dark yellow curves).The left panel represents MDA with IDA and the right one represents DA.For each TAS, we assumed a sample size of 400.